miRNAs have been implicated in schizophrenia. Mutations in genes encoding miRNAs or components in the miRNA biogenesis machinery are associated with increased risk for schizophrenia. It is hypothesized that miRNA expression is aberrant in schizophrenia. Using microarray and quantitative PCR, several groups have examined miRNA expression in postmortem brains of people with schizophrenia, and consistently detected miRNA expression change. However, the findings in the brains have been inconsistent. In this project, we employed the next-generation sequencing technology which offers superior sensitivity and quantifiability to identify miRNAs that are differentially expressed in schizophrenic brains. We also analyzed the effect of psychiatric medications and tobacco smoking on miRNA expression. Using bioinformatics, we found that the targets of miRNAs differentially expressed in schizophrenia are enriched for genes encoding synaptic proteins and those associated with risk for schizophrenia. During this reporting period, we selected a couple of miRNAs altered in people with schizophrenia and expressed them in the prefrontal cortex of mice. We analyzed dendritic spines and behavior in these mice. We also established cultures of human induced pluripotent stem cells (iPSC) and differentiated them into neurons. We expressed and knocked down miRNAs differentially expressed in people with schizophrenia and will examine synapse development in these cells.